2024-11-08
Drug X is a small molecule drug under early-phase clinical investigation to treat Disease Y in pediatric patients (age 2-18 years).
An phase-I single ascending dose (SAD) clinical study has been completed to investigate the PK of drug X, with 50 patients receiving 1, 2, 5, 10 and 20 mg dose of drug X.
A population PK model was developed using these PK data (./wk8/model/hwwk6.mod).
Some efficacy related endpoints were also collected and the clinical team are interested in exploring exposure-response relationships.
The study team is now designing a Phase 2 proof of concept (POC) study, which they plan to use a twice daily dose (BID) dosing. They want to understand what dosage levels are appropriate to test.
Preclinical study shows:
Considering steady-state is achieve after 4 days with BID dosing. The study team is wondering:
At what dose level can we achieve a steady-state Cmin > 1 ug/L in > 80% patients.
At what dose level can we maintain a steady-state Cmax > 15 ug/L in < 20% patients.
Files:
wk10/model/hwwk6.mod: mrgsolve model for Drug X.wk10/ex1.R: R script to implement simulation.wk10/data/pop.csv: population covariate for simulation.Implementation notes:
mod <- mod %>% zero_re(sigma)).wk10/data/pop.csv for population covariates.addl and ii to implement multiple dosing (e.g., BID).rate=-2 to enable the use of dosing duration (D1) in the model.